Welcome Address from CSJ President
Dear Colleagues,
Welcome to our 10th Joint CSJ RSC Symposium on“Chemistry for Complex Biological Systems”.
This RSC-CSJ symposium is held every year based on ourinternational cooperation agreement between the Royal Society of Chemistry; RSC andthe Chemical Society of Japan; CSJ concluded in July 2010 to further our closer andpersonal relationship. So far, this symposium has been held as one of the international
events on the sidelines of the CSJ Annual Meeting.
This year, our joint symposium celebrates its 10th running in total. In
commemoration of this milestone, we try to make a new attempt. We decided to cooperatewith “The 13th symposium on Biorelevant Chemistry” organized by two of CSJ Divisions(Division of Biofunctional Chemistry and Division of Biotechnology) and a grant-aided
academic group titled “Chemistry for Multimolecular Crowding Biosystems”. Prof.
Hamachi, the leader of this academic group supported by MEXT gave a special
consideration to provide a better experience for all of participants from the planning stage.
The purpose of this group is to establish a new chemical approach for functional analysis
and artificial regulation of biological molecules residing in crowded biosystems. Hence,
we set the theme for this RSC-CSJ symposium as “Chemistry for Complex Biological
Systems” after due deliberation. We also carefully selected 10 promising young
researchers both from the UK and Japan, who have been derived from this cutting-edge
field.
Additionally, we invited 33 active Japanese researchers in this specific area toparticipate in our symposium. It is also the first challenge to ask all participants to give aflush presentation as well as poster session to develop the deep and warm personal
relationship with each other.
I would like to thank Professors John Brazier and Shigeki Kiyonaka forbringing in excellent people to the symposium. I believe this opportunity to sit together
at the same table will provide a meaningful chance for sustainable collaboration between
both countries.
Professor Maki Kawai
President of Chemical Society of Japanー1－

Welcome Address from RSC President
Dear Colleagues,
It is my pleasure to welcome you to the 10th UK-Japan
Symposium, celebrating a decade of this series of events jointly heldby our valued partner the Chemical Society of Japan and the Royal Society of Chemistry.
We have worked closely with the Chemical Society of Japan for a number ofyears to support scientific collaboration and exchange between our two countries. In 2010
we formalised our relationship by signing an international cooperation agreement, which
we renewed in 2015.
Interdisciplinary science and collaboration across borders are essential
elements of successful scientific progress. Our theme for this joint symposium –chemistry for complex biological systems – will support and take advantage of both of
those elements.
We hope that the presentations from our Japanese and UK speakers will
stimulate the exchange of ideas and experiences between all participants and we thankeach of the speakers and all the participants for their contributions to this symposium.
We particularly give thanks to Professor Shigeki Kiyonaka of Nagoya
University and Professor Itaru Hamachi of Kyoto University, for their pivotal role inenabling this symposium.
Once again a very warm welcome to what promises to be an exciting scientificevent. I hope that today offers yet more opportunities to build relationships and find newopportunities for researchers from the UK and Japan to collaborate on this important topic.
I wish you all an informative, productive and enjoyable day.

Professor Dame Carol Robinson
President, Royal Society of Chemistryー2－10th RSC-CSJ Joint Symposium– Chemistry for Complex Biological Systems –September 7th, 2019
Tohoku University, Sendai, Japan

9:00 - 09:10

Opening remarks
From the Chemical Society of Japan: Itaru Hamachi, Kyoto University
From the Royal Society of Chemistry: Stephen Rumbelow, Royal Society of Chemistry(Chair: Shinya Tsukiji, Nagoya Institute of Technology)
9:10 - 09:45 [JP1] Shigeki Kiyonaka (Nagoya University)

New Chemogenetic Approaches for Artificially Controlling Neurotransmitter
Receptor Function in Neuronal System
9:45 - 10:20[UK1] Martin Fascione (University of York)

Organocatalyst‐mediated Bioconjugation of Proteins
10:20 - 10:35 Break(Chair: Hiroshi Murakami, Nagoya University)
10:35 - 11:10 [JP2] Yuki Goto (The University of Tokyo)

Artificial In Vitro Biosynthesis for Elaboration of Pseudo‐natural Peptides
11:10 - 11:45 [UK2] Yu-Hsuan Tsai (Cardiff University)

Using Genetically Incorporated Unnatural Amino Acids to Study and Control
Protein Function
11:45 - 12:20 One-min flash talk for poster presentation (31 presenters)
12:20 - 14:20 Lunch & Poster(Chair: Shinsuke Sando, The University of Tokyo)
14:20 - 14:55 [JP3] Shinya Hagihara (RIKEN)

Dissection of Plant Hormone Signaling with Synthetic Molecules
14:55 - 15:30 [UK3] Rebecca Goss (University of St Andrews)

Blending Synthetic Chemistry with Synthetic Biology in vivo to Enable Accessto New to Nature Natural Productsー3－15:30 - 15:45 Break(Chair: Moritoshi Sato, The University of Tokyo)
15:45 - 16:20 [JP4] Kenjiro Hanaoka (The University of Tokyo)

Construction of a Library of Asymmetric Si‐rhodamine Fluorophores and its
Application to Ratiometric Fluorescence Probes for pH
16:20 - 16:55 [UK4] Akane Kawamura (University of Oxford)

Development of Chemical Tools for Epigenetic Proteins
16:55 - 17:10 Break(Chair: Hirohide Saito, Kyoto University)
17:10 - 17:45 [JP5] Hisae Tateishi-Karimata (Konan University)

Role for G‐quadruplexes of Nucleic Acids During Tumor Progression
17:45 - 18:20 [UK5] John Brazier (University of Reading)

Expanding The i‐motif – Why Does Sequence Matter?
18:20 - 18:30 Closing remarks
Shigeki Kiyonaka, Nagoya University
John Brazier, University of Reading

10th RSC-CSJ Joint Symposium is jointly sponsored by the Institute of Multidisciplinary
Research for Advanced Materials; Tohoku University (IMRAM, or Tagen-Ken in Japanese)and Chemistry for Multi-Molecular Crowding Biosytems; MEXT Grant-in-Aid for
Scientific Research on Innovative Areas FY2017-2021

ー4－

Titles for Poster Presentations (in alphabetical order)

Speaker(Family-name-first)

Affiliation

Title of the Poster Presentation

ENDOH, Tamaki

Konan University

RNA-capturing Microsphere Particles (R-CAMPs)
for Optimization of Functional RNAs

FUJIEDA, Nobutaka

Osaka Prefecture University

Artificial Metalloenzymes Bearing a Small Barrel
Protein

FUJITA, Daishi

Kyoto University

Protein Stabilization and Refolding in a
Chaperonin-inspired Synthetic Cage

HAYASHI, Gosuke

Nagoya University

Cysteinylprolyl Imide (CPI) Crypto-thioester for
Chemical Protein Synthesis

HIRAYAMA, Tasuku

Gifu Pharmaceutical
University

Development of Fluorescent Probes ofSubcellular Labile Fe(II)HORI, Yuichiro

Osaka University

Fluorogen/Protein Hybrid Probes for Detection of
RNA Methylation

IMANISHI, Miki

Kyoto University

A Simple Screening System for Inhibitors of m6ARegulatory Enzymes

INABA, Hiroshi

Tottori University

Modulation of Microtubules by Peptide-based
Encapsulation of Nanostructures

ITOH, Yukihiro

Kyoto Prefectural University of Identification of a KDM5C Inhibitor and Its
Medicine
Biological Evaluation

KATSUDA, Yousuke

Kumamoto University

Development of a Novel Tool to Regulate Gene
Expression Level by Short Nucleic Acid
Control of The Formation Process of Polypeptide
Self-assemblies for Understanding Complex
Biological Systems: From Nano-physiology to
Artificial Cells
Establishment of Enzymomics Approach to Screen
Disease-related Alternation of Enzymatic
Functions
Development of Chemical Probes for
Investigating Biomolucular Dynamics in Living
Cells

KISHIMURA, Akihiro

Kyushu University

KOMATSU, Toru

The University of TokyoMIZUKAMI, ShinTohoku University

MURAKAMI, Hiroshi

Nagoya University

TRAP Display for Selection of Synthetic
Antibodies

MURAOKA, Takahiro

Tokyo University ofAgriculture and Technology

Synthetic Promotors of Oxidative Protein Folding

NAGATOISHI Satoru

The University of Tokyo

Biophysics of the Protein-ligand Interactions toRegulate the Protein Functionsー5－

Speaker(Family-name-first)

Affiliation

Title of the Poster Presentation

NAKASE, Ikuhiko

Osaka Prefecture University

Biofunctional Peptide-modified Exosomes for
Intracellular Delivery

NAKATA, Eiji

Kyoto University

DNA Binding Adaptors to Locate Multiple Enzymes
on DNA Scaffold

SAITO, Hirohide

Kyoto University

Synthetic RNA Technologies to Program Cells

SANDO, Shinsuke

The University of Tokyo

Molecular Technologies to Control Cellular
Functions and Fates

SATO, Moritoshi

The University of Tokyo

Manipulating Living Systems by Light

SATO, Shinichi

Tokyo Institute of Technology

Site-selective Antibody Chemical Modification
Using Photocatalyst-proximity Labeling Reaction

SATO, Shinichi

Kyoto University

Live-cell Imaging of Multiple Endogenous mRNAs
with Dhort RNAs and Small Molecules

SHOJI, Osami

Nagoya University

Use of Decoy Molecules to Trick Cytochrome
P450s

TAKEZAWA, Yusuke

The University of Tokyo

Development of Cu(II)-responsive DNAzymes byIntroducing a Metal-mediated Artificial Base Pair

TAKI, Masayasu

Nagoya University

Super-photostable Organelle Markers for Superresolution Imaging

TAMURA, Tomonori

Kyoto University

Organelle-selective Lipid Labeling and Dynamic
Imaging in Living Cells

TSUKIJI, Shinya

Nagoya Institute ofTechnology

Chemical Tools for Controlling Protein
Localization in Living Cells

TSUTSUMI, Hiroshi

Tokyo Institute of Technology

Functionalized Supramolecular Peptide Hydrogelsfor 3D Culture of Cancer Cells

UCHINOMIYA, Shohei

Kyushu University

Live-cell Imaging of Activity of Fatty Acid Beta
Oxidation Pathway with a Fluorescent Probe

Kyushu University

Size- and Morphology-controlled Co-assembly of
Peptide Amphiphiles and Small Molecules for
Intracellular Delivery

WAKABAYASHI, Rie

ー6－

7

10th RCS/CSJ Joint Symposium

Shigeki Kiyonaka
Professor
Department of Biomolecular Chemistry, Graduate School of Engineering,
Nagoya University
Address: Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
Tel: (+81) 52-789-4275
E-mail: kiyonaka@chembio.nagoya-u.ac.jp
Educational Background1998 B.Sc., Kyushu University (supervisor: Profs. Itaru Hamachi and Seiji Shinkai)
2000 M.Sc., Graduate School of Engineering, Kyushu University (supervisor: Profs. Itaru
Hamachi and Seiji Shinkai)
2002 Doctor of Engineering, Graduate School of Engineering, Kyushu University (supervisor:
Prof. Itaru Hamachi)Professional Career2003 PD, National Institute for Physiological Sciences, Japan (Prof. Yasuo Mori laboratory)
2005 Assistant professor, Kyoto University (Prof. Yasuo Mori laboratory)
2012 Associate professor, Kyoto University (Prof. Itaru Hamachi laboratory)
2019 Professor, Nagoya University



Research Interests
1) Visualization of neurotransmitter receptors in neuronal system
2) Development of chemogenetics tools for understanding neuronal networks
3) Understanding cellular events under subcellular or suborganellar resolution



Recent Publications

1. "On-cell coordination chemistry: Chemogenetic activation of membrane-bound glutamate receptors in living
cells", Ryou Kubota, Shigeki Kiyonaka, Itaru Hamachi, Methods Enzymol. 2019, 622, 411.
2. "Ligand-Directed Chemistry of AMPA Receptors Confers Live-Cell Fluorescent Biosensors", Shigeki
Kiyonaka, Seiji Sakamoto ,Sho Wakayama, Yuma Morikawa, Muneo Tsujikawa, Itaru Hamachi, ACS Chem.
Biol. 2018, 13, 1880.
3. "Chemical labeling for visualizing native AMPA receptors in live neurons", Sho Wakayama, Shigeki
Kiyonaka, Itaru Arai, Wataru Kakegawa, Shinji Matsuda, Keiji Ibata, Yuri L. Nemoto, Akihiro Kusumi,
Michisuke Yuzaki, Itaru Hamachi, Nat. Commun. 2017, 8, 14850.
4. "Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living
cells", Shigeki Kiyonaka, Ryou Kubota, Yukiko Michibata, Masayoshi Sakakura, Hideo Takahashi,
Tomohiro Numata, Ryuji Inoue, Michisuke Yuzaki,Itaru Hamachi, Nat. Chem. 2016, 8, 958.
5. "Discovery of allosteric modulators for GABAA receptors by ligand-directed chemistry", Kei Yamaura,
Shigeki Kiyonaka, Tomohiro Numata, Ryuji Inoue, Itaru Hamachi, Nat. Chem. Biol. 2016, 12, 822.
6. "Validating subcellular thermal changes revealed by fluorescent thermosensors", Shigeki Kiyonaka, Reiko
Sakaguchi, Itaru Hamachi, Takashi Morii, Takenao Yoshizakik, Yasuo Mori, Nat. Methods 2015, 12, 801.
7. "Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells",
Shigeki Kiyonaka, Taketoshi Kajimoto, Reiko Sakaguchi, Daisuke Shinmi, Mariko Omatsu-Kanbe, Hiroshi
Matsuura, Hiromi Imamura, Takenao Yoshizaki, Itaru Hamachi, Takashi Morii, Yasuo Mori, Nat. Methods
2013, 10, 1232.

8

Chemistry for Complex Biological System

New Chemogenetic Approaches for Artificially Controlling Neurotransmitter
Receptor Function in Neuronal System
Shigeki Kiyonaka
Department of Biomolecular Chemistry, Graduate School of Engineering, Nagoya University,
Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
Understanding the molecular mechanisms of memory formation is a critically important inneuroscience. Recent studies have revealed that functions of neurotransmitter receptors are
dynamically regulated in the memory formation. In contrast, disregulation of neurotransmitter
receptors causes neurological disorders. For clarifying these mechanisms in brain tissues or live
animals, development of new methods for regulating neurotransmitter receptors in target cells arehighly desired. We have recently reported a new method for selective activation of glutamate
receptors on live cells, by combination of point-mutagenesis with metal complex-mediated molecular
recognition, termed coordination chemogenetics. Our concept relies on stabilization of the active
conformation of the membrane receptors via coordination bonding of Pd2+ complexes with mutatedamino acid residues, which enables allosteric activation of the receptor subtype in target cells. Using
this strategy, chemogenetics activation of ion-channel-type and GPCR-type glutamate receptors has
been successfully carried out in target cells or brain tissue. We expect that this method would beapplicable for understanding neuronal circuits in the brain.

Figure 1. Schematic illustration of coordination chemogenetics for glutamate receptors.

9

10th RCS/CSJ Joint Symposium

Martin Fascione
Assistant Professor of Chemical Biology
York Structural Biology Lab, Department of Chemistry, The University of York
Address: Heslington Road, York, YO10 5DD, UK
Tel & Fax: +44 (0)1904 328822
E-mail: martin.fascione@york.ac.uk


Educational Background2005
MChem., University of Leeds, UK
2009
Ph.D., School of Chemistry, University of Leeds (supervisor: Prof. W. Bruce Turnbull)Professional Career
2009-2012 EPSRC funded postdoctoral research associate, University of Leeds (“carbohydratebinding-protein based virus-like particles”), with Dr. W. Bruce Turnbull
2012-2013 Marie Curie International Outgoing Fellow, University of British Columbia,
Vancouver, Canada (“xylanases as models for understanding enzymatic catalysis”),
with Prof. Stephen G. Withers, FRS
2013-2014 Marie Curie Research Fellow, YSBL, University of York (“mechanistic study ofcarbohydrate processing enzymes using protein semi-synthesis and x-ray
crystallography”), with Prof. Gideon Davies, FMedSci, FRS
Aug 2014-present Lecturer in Chemical Biology, YSBL, Department of Chemistry, University ofYork, UK.



Research Interests
1) Chemical glycobiology2) Bioconjugation chemistry Awards
・ Henry Ellison Scholarship, 2005, University of Leeds
・ JB Cohen Prize, 2010, University of Leeds
・ Marie Curie International Outgoing Research Fellowship 2012-2014


Recent Publications

1. "Using automated glycan assembly (AGA) for the practical synthesis of heparan sulfate oligosaccharide
precursor", Darshita Budhadev, Karinna Saxby, Julia Walton, Gideon Davies, Peter C. Tyler, Ralf
Schworer, Martin A. Fascione, Org. Biomol. Chem. 2019, 17, 1817. DOI: 10.1039/C8OB02756K.
2. "Site-selective C-C modification of proteins at neutral pH using organocatalyst-mediated cross aldol
ligations ", Richard J. Spears, Robin L. Brabham, Darshita Budhadev, Tessa Keenan, Sophie McKenna,
Julia Walton, James. A. Brannigan, A. Marek Brzozowski, Anthony J. Wilkinson, Michael Plevin,
Martin A. Fascione, Chem. Sci. 2018, 9(25), 5585. DOI: 10.1039/c8sc01617h.
3. "Palladium-unleashed proteins: gentle aldehyde decaging for site-selective protein modification", Robin
L. Brabham, Richard J. Spears, Julia Walton, Swati Tyagi, Edward A. Lemke, Martin A. Fascione,
Chem. Commun. 2018, 54, 1501. DOI: 10.1039/C7CC07740H.

10

Chemistry for Complex Biological System

Organocatalyst-mediated Bioconjugation of Proteins
Richard J. Spears,a Robin L. Brabham,a Darshita Budhadev,a Tessa Keenan,a Sphie McKenna,aJulia Walton,a James. A. Brannigan,a A. Marek Brzozowski,a Anthony J. Wilkinson,aMichael Plevin,a, and Martin A. Fascionea,baYork Structural Biology Lab, Department of Chemistry, The University of York,York, United Kingdomb
Department of Biology, The University of York, York, United Kingdom

The bioconjugation of proteins with small molecules has revolutionised the fields of chemical
medicine, chemical biology, and cell biology, enabling scientists to probe and perturb dynamic
cellular processes. The general use of chemical methods for the functionalisation of proteins is still
limited however as they often require complicated reaction partners and/or non-physiological pH,
which is incompatible with many protein scaffolds. Herein we describe efficient organocatalystmediated reaction on proteins using simple chemical probes (Figure 1), which afford a range of stableC-C linked bioconjugates at physiological pH. This strategy is showcased in the ‘chemical mimicry’of a previously inaccessible natural dual post-translationally modified protein, integral to thepathogenesis of the neglected tropical disease Leishmaniasis, and provides a facile route todifferentially modified proteins under biologically compatible conditions.

Figure 1.

11

10th RCS/CSJ Joint Symposium

Yuki Goto
Associate Professor of Chemistry
Department of Chemistry, Graduate School of Science, The University of Tokyo
Address: 7-3-1, Hongo, Bunkyo, Tokyo 113-0033, Japan
Tel: (+81)-3-5841-4338
E-mail: y-goto@chem.s.u-tokyo.ac.jp
Educational Background2003 B.Sc., Kyoto University (supervisor: Prof. Isao Saito)
2005 M.Sc., Graduate School of Engineering, Kyoto University (supervisor: Prof. Kazuhiko Nakatani)2008 Ph.D. in Engineering, Graduate School of Engineering, The University of Tokyo (supervisor:
Prof. Hiroaki Suga)

Professional Career2008 Postdoctoral research associate, University of Illinois at Urbana-Champaign
JSPS Postdoctoral Fellow for Research Abroad (advisor: Prof. Wilfred A. van der Donk)
2009 Assistant professor, The University of Tokyo
2011 PRESTO researcher, JST (cross-appointed)
2016 Associate professor, The University of Tokyo

Research Interests
1) In vitro engineering of biosynthetic pathways for facile synthesis of artificial compounds2) Elaboration of bioactive pseudo-natural peptides

Awards2013 Young Scientists Prize, Minister of Education, Culture, Sports, Science and Technology
2016 Young Investigator Award, Japanese Peptide Society
2017 The Chemical Society of Japan Award For Young Chemists for 20172018 The 1st Bioindustry Research Award

Recent Publications

1.

"Ribosomal Synthesis of Backbone-Cyclic Peptides Compatible with In Vitro Display", Ryo Takatsuji, Koki
Shinbara, Takayuki Katoh, Yuki Goto, Toby Passioura, Ryo Yajima, Yamato Komatsu, Hiroaki Suga, J.
Am. Chem. Soc. 2019, 141, 2279.
"Engineering of RiPP pathways for the production of artificial peptides bearing various non-proteinogenic
structures.", Yuki Goto, Hiroaki Suga, Curr. Opin. Chem. Biol. 2018, 46, 82.
"Dissection of goadsporin biosynthesis by in vitro reconstitution leading to designer analogues expressed invivo", Taro Ozaki, Kona Yamashita, Yuki Goto, Morito Shimomura, Shohei Hayashi, Shumpei Asamizu,
Yoshinori Sugai, Haruo Ikeda, Hiroaki Suga, Hiroyasu Onaka, Nat. Commun. 2017, 8, 14207.
"Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codonboxes", Yoshihiko Iwane, Azusa Hitomi, Hiroshi Murakami, Takayuki Katoh, Yuki Goto, Hiroaki Suga, Nat.
Chem. 2016, 8, 317.
"One-Pot Synthesis of Azoline-Containing Peptides in a Cell-free Translation System Integrated with a
Posttranslational Cyclodehydratase ", Yuki Goto, Yumi Ito, Yasuharu Kato, Shotaro Tsunoda, Hiroaki Suga,
Chem. Biol. 2014, 21, 766.
"Nonstandard Peptide Expression under the Genetic Code Consisting of Reprogrammed Dual Sense
Codons", Yuki Goto, Megumi Iseki, Azusa Hitomi, Hiroshi Murakami, Hiroaki Suga, ACS Chem. Biol.
2014, 8, 2630.

2.
3.
4.
5.
6.

12

Chemistry for Complex Biological System

Artificial In Vitro Biosynthesis for Elaboration of Pseudo-natural Peptides
Yuki Goto
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo,
Tokyo 113-0033, Japan
JST-PRESTO, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033, Japan

Naturally occurring peptides produced as secondary metabolites in microorganisms often havemacrocyclic scaffolds with diverse modified backbone structures such as N-methylated amides,
thioamides, heterocyclic backbones, and β/γ-amino acids. As such unique nonproteinogenic structures
play important roles in diverse bioactivities of the natural peptides, peptides with the non-standard
structures can be attractive candidates even for artificial bioactive peptides.
Many biosynthetic systems involved in the production of macrocyclic scaffolds and modified
backbones have been discovered from nature to date. Although they are useful synthetic tools to
produce specific natural products and their related analogs, it is generally difficult to be applied forthe synthesis of de novo artificial molecules and their chemical libraries. Thus, versatile biosynthetic
systems that facilitate production of diverse and artificial peptides with non-standard peptides had
been demanded for development of novel bioactive peptides.
We have developed artificial in vitro biosynthesis systems by the combination of custom-maderibosomal synthesis (named FIT system) and various posttranslational modification strategies. The
FIT system enables us to reprogram the genetic code to produce peptides with multiple non-canonicalamino acids such as N-methylated amino acids and D-amino acids. We have demonstrated thatchemical and enzymatic posttranslational modification of the resulting peptide successfully yielded
various non-proteinogenic structured found in naturally occurring bioactive peptides. These artificial
in vitro biosynthesis can be applied for construction of natural product-like peptide libraries with thecomplexity of more than a trillion members. By integrating this technology with an in vitro display
system, the peptide libraries with various ring sizes and building blocks can be rapidly screened
against drug targets, resulting in novel bioactive peptides. These works have demonstrated synthetic
and pharmaceutical potentials of the artificial in vitro biosynthesis systems, leading to the elaborationof a new class of bioactive molecules so-called pseudo-natural peptides.

Figure 1. Artificial in vitro biosynthesis systems that can synthesize various pseudo-natural peptides containing
diverse non-proteinogenic structures.

13

10th RCS/CSJ Joint Symposium

Yu-Hsuan Tsai
Lecturer
School of Chemistry, Cardiff University
Address: Main Building, Park Place, Cardiff CF10 3AT, United Kingdom
Tel: (+44)-2920-879285
E-mail: tsaiy5@cardiff.ac.uk


Educational Background2006 B.Sc., National Taiwan University
2008 M.Sc., Department of Chemistry and Applied Biosciences, Swiss Federal Institute ofTechnology Zurich (supervisor: Prof. Peter H. Seeberger)
2001 Doctor of Natural Science, Division of Biology, Chemistry, Pharmacy, Freie Universität
Berlin (supervisor: Prof. Peter H. Seeberger)Professional Career2006 - 2007 Research Assistant, Academia Sinica (Taipei, Taiwan)
2012 - 2014 Postdoc, Medical Research Council Laboratory of Molecular Biology (Cambridge,
England)2015 - now Lecturer, Cardiff University (Cardiff, Wales)Research Interests
1) Novel approaches for protein modulation
2) Protein post-translational modification in bacteria

Awards2001 Chinese Chemical Society Award
2012 MRC Career Development Fellowship2017 GW4 Crucible
2018 British Science Association Media Fellowship

Recent Publications
1. "Selective, rapid and optically switchable regulation of protein function in live mammalian cells", YuHsuan Tsai, Sebastian Essig, John R. James, Kathrin Lang, Jason W. Chin, Nat. Chem. 2015, 7, 554.
2. Acetylome of Acinetobacter baumannii SK17 Reveals a Highly-Conserved Modification of Histonelike Protein HU", Jiahn-Haur Liao, Cheng-Han Tsai, Sanjay G. Patel, Jhih-Tian Yang, I-Fan Tu, Matteo
Lo Cicero, Magdalena Lipka-Lloyd, Wan-Ling Wu, Wen-Jie Shen, Meng-Ru Ho, Chi-Chi Chou,
Garima R. Sharma, Hiroki Okanishi, Louis Y. P. Luk, Yu-Hsuan Tsai*, Shih-Hsiung Wu*, Front. Mol.
Biosci. 2017, 4, 77. DOI: 10.3389/fmolb.2017.00077.
3. "Switchable genome editing via genetic code expansion", Toru Suzuki, Maki Asami, Sanjay G. Patel,Louis Y. P. Luk, Yu-Hsuan Tsai, Anthony C. F. Perry, Sci. Rep. 2018, 8, 10051.
4. "Using genetically incorporated unnatural amino acids to control protein functions in mammalian cells",
Alexander R. Nodling, Luke A. Spear, Thomas L. Williams, Louis Y. P. Luk, Yu-Hsuan Tsai, Essays
Biochem. 2019, 63, in press (DOI: 10.1042/EBC20180042).

14

Chemistry for Complex Biological System

Using Genetically Incorporated Unnatural Amino Acids to Studyand Control Protein Function
Yu-Hsuan Tsai
School of Chemistry, Cardiff University, Cardiff CF10 3AT, United Kingdom

Genetic code expansion (Figure 1) allows unnatural (non-canonical) amino acid incorporation into
proteins of interest by repurposing the cellular translation machinery.1 The development of thistechnique has enabled site-specific incorporation of many structurally and chemically diverse aminoacids, facilitating a plethora of applications. Here I will show how genetic code expansion can beapplied to regulate protein function in mammalian cells2 and study protein post-translational
modification.3

Figure 1. Concept of genetic code expansion.

References:
1. "Using genetically incorporated unnatural amino acids to control protein functions inmammalian cells", A. R. Nödling, L. A. Spear, T. L. Williams, L. Y. P. Luk, Y.-H. Tsai, Essays
Biochem. 2019, 63, DOI: 10.1042/EBC20180042.
2. (a) "Selective, rapid and optically switchable regulation of protein function in live mammaliancells", Yu-Hsuan Tsai, Sebastian Essig, John R. James, Kathrin Lang, Jason W. Chin, Nat.
Chem. 2015, 7, 554.
(b) "Switchable genome editing via genetic code expansion", Toru Suzuki, Maki Asami, Sanjay
G. Patel, Louis Y. P. Luk, Yu-Hsuan Tsai, Anthony C. F. Perry, Sci. Rep. 2018, 8, 10051.
3. "Acetylome of Acinetobacter baumannii SK17 Reveals a Highly-Conserved Modification ofHistone-Like Protein HU", Jiahn-Haur Liao, Cheng-Han Tsai, Sanjay G. Patel, Jhih-Tian Yang,
I-Fan Tu, Matteo Lo Cicero, Magdalena Lipka-Lloyd, Wan-Ling Wu, Wen-Jie Shen, Meng-Ru
Ho, Chi-Chi Chou, Garima R. Sharma, Hiroki Okanishi, Louis Y. P. Luk, Yu-Hsuan Tsai*,
Shih-Hsiung Wu*, Front. Mol. Biosci. 2017, 4, 77.

15

10th RCS/CSJ Joint Symposium

Shinya Hagihara
Team Leader
Center for Sustainable Resource Science, RIKEN
Address: 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Tel & Fax: (+81)-48-467-9772
E-mail: hagi@riken.jp
Educational Background1998 B.Eng., Kyoto University (supervisor: Prof. Isao Saito)
2000 M.Eng., Graduate School of Engineering, Kyoto University (supervisor: Prof. Isao Saito)
2003 Doctor of Engineering, Graduate School of Engineering, Kyoto University (supervisor:
Prof. Isao Saito)

 Professional Career2003 RIKEN (PD)2007 University of Geneva (PD)2008 Assistant professor, Tohoku University
2013 Associate professor, Nagoya University
2018 Team Leader, RIKEN Research Interests
Plant chemical biology
 Awards
2015 Lecture Award, Bio-related Chemistry Symposium
2018 Mishima Kaiun Memorial Award

Recent Publications

1. "Chemical hijacking of auxin signaling with an engineered auxin-TIR1 pair ", Naoyuki Uchida, Koji
Takahashi, Rie Iwasaki, Ryotaro Yamada, Masahiko Yoshimura, Takaho A. Endo, Seisuke Kimura,
Hua Zhang, Mika Nomoto, Yasuomi Tada, Toshinori Kinoshita, Kenichiro Itami, Shinya Hagihara,
Keiko U. Torii, Nat. Chem. Biol. 2018, 14, 299.
2. "A super strong engineered auxin-TIR1 pair ", Ryotaro Yamada, Keiichiro Murai, Naoyuki Uchida,
Koji Takahashi, Rie Iwasaki, Yasuomi Tada, Toshinori Kinoshita, Kenichiro Itami, Keiko U. Torii,
Shinya Hagihara, Plant Cell Physiol. 2018, 59, 1538.
3. "Rapid and reversible root growth inhibition by TIR1 auxin signalling ", Matyáš Fendrych, Maria
Akhmanova, Jack Merrin, Matouš Glanc, Shinya Hagihara, Koji Takahashi, Naoyuki Uchida, Keiko U.
Torii, Jiří Friml, Nat. Plants 2018, 4, 453.
4. "Probing strigolactone receptors in Striga hermonthica with fluorescence ", Yuichiro Tsuchiya,
Masahiko Yoshimura, Yoshikatsu Sato, Keiko Kuwata, Shigeo Toh, Duncan Holbrook-Smith, Hua
Zhang, Peter McCourt, Kenichiro Itami, Toshinori Kinoshita, Shinya Hagihara, Science 2015, 349, 864.

16

Chemistry for Complex Biological System

Dissection of Plant Hormone Signaling with Synthetic Molecules
Shinya Hagihara a,baCenter for Sustainable Resource Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japanb
Institute of Transformative Bio-Molecules, Nagoya University, Furo-cho, Chikusa-ku, Nagoya
464-8601, Japan

Molecular recognition in miscellaneous and crowding multimolecular biosystems plays an importantrole in biological functions. Especially, the specific interaction between plant hormone and its
receptor protein is crucial for long-distance signal transduction that enables plants to rapidly adapt toenvironmental changes. Although recent biological studies have made substantial progress in our
understanding of plant hormone signaling, delineating plant hormone response at molecular levelremains a major challenge. In this presentation, we will show chemistry-based approaches tounderstand and regulate plant hormone signaling. Our studies successfully uncovered long-soughtafter mechanism of auxin signaling.

17

10th RCS/CSJ Joint Symposium

Rebecca Jane Miriam Goss
Professor of Organic/Biomolecular Chemistry
Department of Chemistry, The University of St Andrews, Scotland
Address: School of Chemistry, Biomolecular Sciences Building,North Haugh, St Andrews, KY16 9ST, United Kingdom
Tel: +44 (0)1334 463856
E-mail: rjmg@st-andrews.ac.uk


Educational Background1997 Degree Chemistry BSc Hons., University of Durham, UK
2001 PhD, School of Chemistry, University of Durham (supervisor: Prof. David O’Hagan)Professional Career2000 Postdoctoral Research Associate, (Professors Staunton FRS and Leadlay FRS) University of Cambridge
2002 Teaching Fellow, School of Chemistry, University of Nottingham
2003 Proleptic lectureship University of Exeter
2005 Lecturer, then Senior Lecturer, then Reader, University of East Anglia
2012 Reader then Professor, School of Chemistry, University of St Andrews



Research Interests

1)
2)
3)

Blending synthetic biology with synthetic chemistry to make new to nature natural products of medicinal
relevance
Biosynthetic elucidation of complex natural products
Developing Enzymes for SynthesisAwards and Honours

2003 Royal Society Dorothy Hodgkin Fellowship (~10 awarded each year across the UK in science)
2007 awarded the 2006 RSC Meldola Medal (awarded to the most promising UK chemist under the age of 32)
in particular I was “distinguished for excellent contributions at the interface of organic chemistry andmolecular biology”
2011 Thieme Chemistry Journal Award
2011 JSP award to participate at the Burgenstock Stereochemistry meeting2011 Selected as the UK’s under 40 Organic Chemistry delegate for EuCheM’s Young Investigators Workshop
2013 Natural Product Report Emerging Researcher Lectureship*Awarded for our pioneering new approach to natural product analogue generation “Genochemetics”, whichmarries together Synthetic Biology and Synthetic Chemistry to access new bioactives of medicinal interest.
2017-onwards Associate Editor for Chem. Soc. Rev.
 Recent Publications
1. "A natural solution to the photoprotection and isolation of the potent polyene antibiotic marinomycin",
Christopher S. Bailey, Joseph S. Zarins-Tutt, Matthias Agbo, Hong Gao, Alberto Diego Taboada, Maoluo
Gan, Emily R. Abraham, Grahame Mackenzie, P. Andrew Evans, Rebecca J. M. Goss, Chem. Sci. 2019,
DOI: 10.1039/C9SC01375J. (*Chem Sci Pick of the week, Highlighted in C&EN News.
https://cen.acs.org/pharmaceuticals/Pollen-shells-protect-drugs-UV/97/i22)
2. "Heck Diversification of Indole-Based Substrates under Aqueous Conditions: From Indoles to Unprotected
Halo-tryptophans and Halo-tryptophans in Natural Product Derivatives", Cristina Pubill-Ulldemolins, Sunil
V. Sharma, Christopher Cartmell, Jinlian Zhao, Paco Cμrdenas, Rebecca J. M. Goss, Chem. Eur. J. 2019,
DOI: 10.1002/chem.20190137.
3. "Buchwald Hartwig diversification of unprotected halotryptophans, halotryptophan containing tripeptides
and the natural product barettin in aqueous conditions", Yohann J. G. Renault, Rosemary Lynch, Enrico
Marelli, Sunil. V. Sharma, Cristina Pubill-Ulldemolins, Joshua A. Sharp, Chris Cartmell, Paco Cárdenas,
Rebecca J. M. Goss, Chem. Commun. 2019, accepted.

18

Chemistry for Complex Biological System

Blending Synthetic Chemistry with Synthetic Biology in vivo to Enable Accessto New to Nature Natural Products
Rebecca J. M. Goss
School of Chemistry, University of St Andrews, Fife, Scotland, UK KY169ST, United Kingdom
Natural products represent a treasure trove of medicinally relevant compounds: over the past 3 decades over 70%
of antimicrobials and over 60% of antitumor agents entering clinical trials have been based on natural products.
Generation of natural product analogues is an important area.
We have pioneered a new concept in which a gene is introduced to an organism and coerced to work in concert withan existing biosynthetic pathway. This installs a chemical handle that enables selective derivatisation of the natural
product.1-4 The selective modification of the new to nature natural product in the presence of the living cells that
produce it will also be discussed.5

Scheme 1: GenoChemetics; gene insertion enables the installation of a reactive and chemicallyorthogonal handle into a natural product, permitting its selective functionalization and diversification.
References:
1. Abhijeet Deb Roy, Sabine Gruschow, Nickiwe Cairns, Rebecca J. M. Goss, J. Am. Chem. Soc. 2010, 132(35), 12243.
2. M. J. Corr, S. V. Sharma, C. Pubill-Ulldemolins, R. T. Bown, P. Poirot, D. R. M. Smith, C. Cartmell, A. Abou Fayad,
R. J. M. Goss, Chem. Sci. 2017, 7, 2039. DOI: 10.1039/c6sc04423a (Edge Article).
3. Duncan R. M. Smith, Agustinus R. Uria, Eric J. N. Helfrich, Daniela Milbredt, Karl-Heinz van PeeJorn Piel,
Rebecca J. M. Goss, ACS Chem. Biol. 2017, 12(5), 1281.
4. Enrico Marelli, Yohann Renault, Sunil V. Sharma, Steven P. Nolan, Rebecca J. M. Goss, Chem. Eur. J. 2017, 23,3832. DOI:10.1002/chem.201700680.
5. Sunil V. Sharma, Xiaoxue Tong, Cristina Pubill-Ulldemolins, Christopher Cartmell, Emma J. A. Bogosyan, Emma J.
Rackham, Enrico Marelli, Refaat B. Hamed, Rebecca J. M. Goss, Nat. Commun. 2017, 8, 229. DOI:
10.1038/s41467-017-00194-3.

19

10th RCS/CSJ Joint Symposium

Kenjiro Hanaoka
Associate Professor
Graduate School of Pharmaceutical Sciences, The University of Tokyo
Address: 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Tel : (+81)-3-5841-4852
Fax: (+81)-3-5841-4855
E-mail: khanaoka@mol.f.u-tokyo.ac.jp
Educational Background2000 B.Sc., Faculty of Pharmaceutical Sciences, The University of Tokyo (supervisor: Prof. Tetsuo Nagano)2002 M.Sc., Graduate School of Pharmaceutical Sciences, The University of Tokyo (supervisor: Prof.
Tetsuo Nagano)2005 Doctor of Pharmacy, Graduate School of Pharmaceutical Sciences, The University of Tokyo(supervisor: Prof. Tetsuo Nagano)Professional Career2004 Research Fellow of the Japan Society for the Promotion of Science (JSPS Research Fellow) (DC2)2005 Postdoctoral Fellow, University of Texas, Southwestern Medical Center, USA (supervisor: Prof. Thomas
Kodadek)
2006 Research Fellow of the Japan Society for the Promotion of Science (JSPS Research Fellow) (SPD)2007 Assistant professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo
2010 Lecturer, Graduate School of Pharmaceutical Sciences, The University of Tokyo
2011 Associate professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo

Research Interests

1) Fluorescence probes
2) Chemical tools for bioimaging and drug discovery

Awards2010 The Pharmaceutical Society of Japan Award for Young Scientists
2011 The Young Scientists’ Prize, The Commendation for Science and Technology, by the Minister of Education,
Culture, Sports, Science and Technology
2011 Inoue Science Research Award
2014 Nakatani Foundation Award
2014 ICBS Young Chemical Biologist Award (The International Chemical Biology Society)

Recent Publications

1. "Design and Synthesis of an Activatable Photoacoustic Probe for Hypochlorous Acid", Takayuki Ikeno, Kenjiro
Hanaoka*, Shimpei Iwaki, Takuya Myochin, Yoshiaki Murayama, Hisashi Ohde, Toru Komatsu, Tasuku Ueno,
Tetsuo Nagano, Yasuteru Urano*, Anal. Chem. in press.
2. "Synthesis of unsymmetrical Si-rhodamine fluorophores and application to a far-red to near-infrared
fluorescence probe for hypoxia", Kenjiro Hanaoka*, Yu Kagami, Wen Piao, Takuya Myochin, Koji Numasawa,
Yugo Kuriki, Takayuki Ikeno, Tasuku Ueno, Toru Komatsu, Takuya Terai, Tetsuo Nagano, Yasuteru
Urano*, Chem. Commun. 2018, 54, 6939.
3. "Development of a Series of Practical Fluorescent Chemical Tools to Measure pH Values in Living Samples",Shodai Takahashi, Yu Kagami, Kenjiro Hanaoka*, Takuya Terai, Toru Komatsu, Tasuku Ueno, Masanobu
Uchiyama, Ikuko Koyama-Honda, Noboru Mizushima, Tomohiko Taguchi, Hiroyuki Arai, Tetsuo Nagano,
Yasuteru Urano*, J. Am. Chem. Soc. 2018, 140, 5925.

20

Chemistry for Complex Biological System

Construction of a Library of Asymmetric Si-rhodamine Fluorophores andits Application to Ratiometric Fluorescence Probes for pH
Kenjiro Hanaoka
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Red to NIR-fluorescent Si-rhodamines (SiRs) are favorable long-wavelength fluorophores forbioimaging that retain the advantageous photophysical properties of conventional rhodamine dyes
such as high photostability and high quantum yield (see our review article: Chem. Asian J., 2017, 12,1435). However, their chemical structures are limited to symmetrical ones, so further derivatizationof the structure would expand the molecular design and applicable range of fluorescence probes basedon SiRs. For this purpose, we newly developed a novel synthetic method of 4,4’-methylenebisaniline
derivatives, and we successfully achieved the synthesis of various asymmetrical SiRs by using thisreaction as a key step for constructing SiR fluorophores (Chem. Commun. 2018, 54, 6939).
Among synthesized asymmetric SiRs, we luckily discovered a compound that shows anabsorption wavelength change of about 80 nm in response to pH change. We considered that this SiR
scaffold could be an excellent scaffold for developing fluorescence probes for ratiometric pH
measurements, because modification of the pKa value and the absorption and emission wavelengths,
as well as introduction of functional groups, can be easily performed. In biological systems, the pH
in intracellular organelles is strictly regulated, and differences of pH are deeply related to key
biological events such as protein degradation and intracellular trafficking. Ratiometric fluorescenceimaging is useful for determination of precise pH values, but existing fluorescence probes havesubstantial limitations, such as inappropriate pKa for imaging in the physiological pH range,
inadequate photobleaching resistance, and insufficiently long excitation and emission wavelengths.
So, we developed a versatile scaffold for ratiometric fluorescence pH probes, based on the abovementioned pH-sensitive asymmetric SiR (J. Am. Chem. Soc. 2018, 140, 5925). We developed
SiRpH6.1 as a ratiometric pH fluorescence probe, and it has suitable pKa and water solubility for
imaging in acidic intracellular compartments; by using transferrin tagged with SiRpH6.1, we
achieved time-lapse imaging of pH in endocytic compartments during protein trafficking for the firsttime. These chemical tools should be useful for studying the influence of intracellular pH on
biological processes.
SiRpH6.1
Ex/Em = 620/638 nm
Φf l = 0.21

Ex/Em = 637/660 nm
Φf l = 0.18

Ex/Em = 654/672 nm
Φf l = 0.24

Ex/Em = 675/698 nm
Φf l = 0.07

Ex/Em = 666/684 nm
Φf l = 0.25

Ex/Em = 670/687 nm
Φf l = 0.27

pKa = 6.1
Ex/Em = 671/687 nm
Φf l = 0.29

Ex/Em = 596/676 nm
Φf l = 0.21

ε580 x Φfl (pH 4.5) = 4.8 x 103
ε663 x Φfl (pH 8.0) = 3.6 x 103

Photophysical properties were measured in 100 mM NaPi buffer (pH 7.4).

Figure 1. Established synthetic scheme for asymmetrical SiRs and their photophysical properties. Based on
the synthesized asymmetrical SiR, a new ratiometric fluorescence probe for pH, SiRpH6.1, has beendeveloped.

21

10th RCS/CSJ Joint Symposium

Akane Kawamura
Associate Professor in Chemical Biology
Department of Chemistry, Chemistry Research Laboratory,
University of Oxford
Address: 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom
Tel: (+44) 1865 275910 (office)E-mail: akane.kawamura@chem.ox.ac.uk


Educational Background2000 M.Chem (Hons), University of Oxford
2005 D.Phil Pharmacology, University of Oxford (supervisor: Prof Edith Sim)

Professional Career2006 Summit Therapeutics PLC (formerly VASTox PLC), Senior Scientist
2009 Senior Postdoctoral Research Assistant, University of Oxford (Prof. Chris Schofield)
2012 BHF CRE Senior Fellow, University of Oxford
2013 Royal Society Dorothy Hodgkin Fellow, University of Oxford
2016 University Research Lecturer, University of Oxford
2019 Associate Professor, University of Oxford

Research Interests
1) Development of chemical probes / tools for studying enzymes involved in epigenetic
regulation
2) Biochemical and functional studies of histone demethylases
3) Peptide-based inhibitor design



Recent Publications

1. "Non-competitive cyclic peptides for targeting enzyme-substrate complexes", T. E. McAllister, T.-L. Yeh, M.
I. Abboud, I. K. H. Leung, E. S. Hookway, O. N. F. King, B. Bhushan, S. T. Williams, R. J. Hopkinson, M.
Münzel, N. D. Loik, R. Chowdhury, U. Oppermann, T. D. W. Claridge, Y. Goto, H. Suga, C. J. Schofield, A.
Kawamura, Chem. Sci. 2018, 9, 4569. DOI: 10.1039/C8SC00286J.
2. "Highly selective inhibition of histone demethylases by de novo macrocyclic peptides", Akane Kawamura,Martin Münzel, Tatsuya Kojima, Clarence Yapp, Bhaskar Bhushan, Yuki Goto, Anthony Tumber, Takayuki
Katoh, Oliver N. F. King, Toby Passioura, Louise J. Walport, Stephanie B. Hatch, Sarah Madden, Susanne
Müller, Paul E. Brennan, Rasheduzzaman Chowdhury, Richard J. Hopkinson, Hiroaki Suga, Christopher J.
Schofield, Nat. Commun. 2017, 8, 14773. DOI: 10.1038/ncomms14773.
3. "The Activity of JmjC Histone Lysine Demethylase KDM4A is Highly Sensitive to Oxygen Concentrations",
Rebecca L. Hancock, Norma Masson, Kate Dunne, Emily Flashman, Akane Kawamura, ACS Chem. Biol.
2017 12(4), 1011. DOI: 10.1021/acschembio.6b00958.
4. "Recent Progress in Histone Demethylase Inhibitors", Tom E. McAllister, Katherine S. England, Richard J.
Hopkinson, Paul E. Brennan, Akane Kawamura, J. Med. Chem. 2016, 59(4),1308. DOI:
10.1021/acs.jmedchem.5b01758.
5. "Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases", Louise J. Walport,
Richard J. Hopkinson, Rasheduzzaman Chowdhury, Rachel Schiller, Wei Ge, Akane Kawamura, Christopher
J. Schofield, Nat. Commun. 2016, 7, 11974. DOI: 10.1038/ncomms11974.

Chemistry for Complex Biological System

Development of Chemical Tools for Epigenetic Proteins
Akane Kawamura
University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA,
United Kingdom
Post-translational modifications (PTMs) on histone tails are of central importance in regulation of gene
expression. Histone PTMs are dynamically modified and recognised by a wide range of epigenetic
proteins. Abnormal histone modification patterns and dysregulation of epigenetic proteins are
implicated in many diseases. Thus, there is significant interest in developing chemical tools to probe
the biology of these epigenetic proteins. Methylation of lysines on histones is reversible, and regulated
by histone methyltransferases (KMTs) and demethylases (KDMs). Despite the emerging importanceof KDMs in cellular processes and the intense therapeutic interest in relation to diseases, developing
chemical tools for KDMs have been challenging. The talk will provide an overview of our recent work
on KDMs, with a particular focus on peptide-based strategies to develop chemical and mechanistic
probes.

22

23

10th RCS/CSJ Joint Symposium

Hisae Tateishi-Karimata
Assistant Professor (Lecturer) of Frontier Institute for
Biomolecular Engineering Research (FIBER)
Konan University
Address: 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047,
Japan
Tel : (+81)-78-303-1443, Fax: (+81)-78-303-1495
E-mail: tateishi@konan-u.ac.jp
Educational Background2003 B.Sc., Faculty of Science, Department of Chemistry, Konan University (supervisor: Prof. Naoki
Sugimoto)
2005 M.Sc., Graduate School of Natural Science, Chemistry, Konan University (supervisor: Prof. Naoki
Sugimoto)
2001 Doctor of Science, Graduate School of Natural Science, Life and Functional Material Science,
Konan University (supervisor: Prof. Naoki Sugimoto)Professional Career
2005.4-2008.3
2008.4-2009.2
2008.4-2008.6
2010.72016.4

Research Fellow, Japan Society for the Promotion of Science, Japan
Researcher, Fine Co. Ltd., Japan
Visiting postdoctoral researcher, University of Illinois, USA
Assistant Professor of Frontier Institute for Biomolecular Engineering Research(FIBER), Konan University
Lecturer of Frontier Institute for Biomolecular Engineering Research (FIBER),
Konan University

Research Interests
1) Nucleic Acid Chemistry2) Biochemistry and BiofunctionalchemistryAwards
2014 Lecture Award, The 95th CSJ (the Chemical Society of Japan) Annual Meeting2014 Lecture Award, Bio-Related Chemistry Symposium2017 Shiseido Science Grant Award
2019 CSJ award for Outstanding Young Women Chemist

Recent Publications
1. "A–T base pairs are more stable than G–C base pairs in a hydrated ionic liquid", Tateishi-Karimata
H, Sugimoto N., Angew. Chem. Int. Ed. 2012, 51, 1416.
2. "i-Motifs are more stable than G-quadruplexes in a hydrated ionic liquid", Hisae Tateishi-Karimata,Miki Nakano, Smritimoy Pramanik, Shigenori Tanaka, Naoki Sugimoto, Chem. Commun. 2015, 51,
6909.
3. "Newly characterized interaction stabilizes DNA structure: oligoethylene glycols stabilize Gquadruplexes CH–π interactions ", Hisae Tateishi-Karimata, Tatsuya Ohyama, Takahiro Muraoka,
Peter Podbevsek, Adam M. Wawro, Shigenori Tanaka, Shu-ichi Nakano, Kazushi Kinbara, Janez
Plavec, Naoki Sugimoto, Nucleic Acids Res. 2017, 45, 7021.
4. "Destabilization of DNA G-Quadruplexes by Chemical Environment Changes during Tumor
Progression Facilitates Transcription", Hisae Tateishi-Karimata, Keiko Kawauchi, Naoki Sugimoto,J. Am. Chem. Soc. 2018, 140, 642.

Chemistry for Complex Biological System

Role for G-quadruplexes of Nucleic Acids During Tumor Progression
Hisae Tateishi-Karimataa and Naoki Sugimotoa,ba

Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University,
17-1-20 Minatojima-minamimachi, Kobe, 650-0047, Japanb
Graduate School of Innovative Research in Science and Technology (FIRST), Konan University,
17-1-20 Minatojima-minamimachi, Kobe, 650-0047, JapanThe DNA structures adopted are affected by their surrounding environments. The canonical DNA structure isa duplex; however, DNA can also form noncanonical structures of triplexes, G-quadruplexes, and cruciforms.
The highly crowded intracellular environments mimicked by cosolutes such as polyethylene glycol (PEG)
and stabilize noncanonical DNA structures and destabilize duplexes suggesting that noncanonical DNAs
should have important roles in cells. Previous reports indicated that transcription by arrested or slipped prior
to the formation of stable structures such as Z-form duplexes, triplexes, and G-quadruplexes in templateDNA. We previously showed that the frequency of mutations resulting from arrest and slippage depends on
the stability of the G-quadruplexes formed in the template DNAs. There are 300,000 sequences with thepotential to form G-quadruplex structures in the human genome, with most of these sequences located inoncogenes or proto-oncogenes. G-quadruplex formation is highly responsive to surrounding conditions,particularly K+ concentration. Malignant cancer cells have a much lower K+ concentration than normal cells
because of overexpression of a K+ channel; thus, G-quadruplexes may be unstable in cancer cells. Here, weinvestigated physicochemically how changes of intracellular chemical environments influence G-quadruplex
formation and transcription during tumor progression in vitro and in cells. In vitro, the stable G-quadruplex
formation inhibits transcription in a solution containing 150 mM KCl (normal condition). As K+
concentration decreases, which decreases G-quadruplex stability, transcript production from templates with

Figure 1. Schematic illustration of effects of G-quadruplex formation on transcription.
G-quadruplex-forming potential increases. In normal cells, the trend in transcript productions was similar tothat in experiments in vitro, that is, transcription efficiency inversely correlated with G-quadruplex stability.
Interestingly, higher transcript levels were produced from templates with G-quadruplex-forming potential in
Ras-transformed and highly metastatic breast cancer cells (MDA-MB-231) than in non-transformed andcontrol MCF-7 cells. These results suggest that in normal cells, K+ ions attenuate the transcription of certain
oncogenes by stabilizing G-quadruplex structures (Figure 1). The G-quadruplex-forming sequences at cancer
related genes are located mainly in non-coding DNA region suggesting that the G-quadruplexes would haveimportant roles during tumor progression.
Acknowledgment: This research was supported by Grants-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT) and Japan Society for the Promotion of Science (JSPS),
especially a Grant-in-Aid for Scientific Research on Innovative Areas “Chemistry for Multimolecular Crowding
Biosystems” (JSPS KAKENHI Grant No. JP17H06351), and Grant-in-Aid for Scientific Research (C)(JP17K05941),
Japan, Shiseido Female Researcher Science Grant, and Kawanishi Memorial Shinmaywa Education Foundation.

24

25

10th RCS/CSJ Joint SymposiumJohn Brazier
Associate Professor of Pharmaceutical Chemistry
Head of Pharmaceutics and Pharmaceutical Chemistry
Department of Pharmacy, University of Reading
Address: Chemistry/ Pharmacy Building, Whiteknights, PO Box 224,
Reading, RG6 6AD, United Kingdom
Tel & Fax: (+44)-(0)118-378-4707
E-mail: j.a.brazier@reading.ac.uk



Educational Background1999 MChem. Chemistry, University of Warwick
2004 PhD. Nucleic Acid Chemistry, University of Sheffield (supervisor: Dr. David Williams)

Professional Career2004 Postdoctoral Research Assistant, University of Liverpool (Prof. Rick Cosstick)
2006 JSPS Postdoctoral Research Fellow, Kyushu University (Prof Shigeki Sasaki)
2008 Lecturer in Pharmaceutical Chemistry, University of Reading2017 Associate Professor in Pharmaceutical Chemistry, University of Reading2017 Head of Pharmaceutics and Pharmaceutical Chemistry, Reading School of Pharmacy,
University of Reading Research Interests
1) Nucleic Acid structure and function, in particular, the structure and function of i-motifs
2) Ruthenium complex binding to nucleic acid structures, including duplexes and higher order
structures


Recent Publications

1. "Structural Studies Reveal Enantiospecific Recognition of a DNA G-Quadruplex by a Ruthenium
Polypyridyl Complex", Kane McQuaid, Holly Abell, Sarah P. Gurung, David R. Allan, Graeme Winter,
Thomas Sorensen, David J. Cardin, John A. Brazier, Christine J. Cardin, James P. Hall, Angew. Chem.
Int. Ed. 2019, DOI:10.1002/anie.201814502.
2. "Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase",
Shuntaro Takahashi, John A. Brazier, Naoki Sugimoto, PNAS 2017, 114 (36), 9605.
3. "The importance of loop length on the stability of i-motif structures", Gurung, S. P., Schwarz, C., Hall,
J. P., Cardin, C. J. and Brazier, J. A. Chem. Commun. 2015, 51(26), 5630.
4. "I-Motif formation in gene promoters: unusually stable formation in sequences complementary toknown G-quadruplexes", John A. Brazier,* Arti Shaha, Geoffrey D. Brown, Chem. Commun. 2012, 48(87), 10739.

Chemistry for Complex Biological System

Expanding The i-motif –Why Does Sequence Matter?
John A. Brazier,a James P. Hall,a and Christine J. CardinbaDepartment of Pharmacy, University of Reading, Reading, RG6 6AD, United Kingdom
Department of Chemistry, University of Reading, Reading, RG6 6AD, United Kingdomb

The i-motif is quadruplex structure that is formed by cytosine-rich sequences of DNA and isformed of cytosine: cytosine basepairs (Figure 1). Recently, the presence of the i-motif in the
nucleus of human cells has been demonstrated using an antibody selected for its specificity
to the i-motif structure.1

Figure 1. a) protonated-cytosine: cytosine base pair b) Schematic representation of an i-motif structure, where
N denotes any DNA heterocyclic base.

This recent finding, along with the evidence that shows the role of the i-motif in modulating gene
expression2 and its ability to inhibit polymerases,3 shows the importance in understanding more about
this unusual structure. It is known from research on biologically derived sequences, that i-motifs
formed by different sequences exhibit different thermal and pH stability.
We are interested in understanding how sequence plays a role in stability, and whether we can use
sequence to provide recognition sites for binding events, whether that is small molecules, or larger
biomolecules. We have shown that longer loops are inherently less stable than short loops,4 but wehave recently demonstrated that long loops provide a suitable binding area for a metal complex,5 andcould therefore be targeted and stabilized by binding molecules. We have also begun to understandthat the requirement for 4 continuous cytosine tracts is not always required for i-motif formation andthat these can be interrupted by non-cytosine bases.6
References:

1. Mahdi Zeraati, David B. Langley, Peter Schofield, Aaron L. Moye, Romain Rouet, William E. Hughes,
Tracy M. Bryan, Marcel E. Dinger, Daniel Christ, Nat. Chem. 2018, 10, 631, DOI: 10.1038/
s41557-018-0046-3.
2. Samantha Kendrick, Hyun-Jin Kang, Mohammad P. Alam, Manikandadas M. Madathil, Prashansa
Agrawal, Vijay Gokhale, Danzhou Yang, Sidney M. Hecht, Laurence H. Hurley, J. Am. Chem. Soc.
2014, 136 (11), 4161, DOI: 10.1021/ja410934b.
3. Shuntaro Takahashi, John A. Brazier, Naoki Sugimoto, PNAS 2017, 114 (36), 9605.
4. Gurung, S. P., Schwarz, C., Hall, J. P., Cardin, C. J., Brazier, J. A., Chem. Commun. 2015, 51(26),5630.
5. Benjamin J. Pages, Sarah P. Gurung, Kane Mcquaid, James P. Hall, David Cardin, Graeme Winter,
Thomas Sorensen, Christine J. Cardin, John A. Brazier*, Manuscript in preparation.
6. Julian Steinhoegl, Alan John, James P. Hall, John A. Brazier, Manuscript in preparation.

26

“If” we publish your profound work,“IF (Impact Factor)” will rise to a new level.
We look forward to your submission.
Chem. Lett. and BCSJ